1-methoxybutane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.2 g) was dissolved in absolute THF (30 ml) and stirred at 0° C. with lithium hexamethyldisilazide (721 μl; density: 0.8 g/1; 23% in tent-butyl methyl ether) for 30 min. At 0° C., methylmagnesium bromide (2.87 ml, 3 M in diethyl ether) was then added dropwise while stirring. After stirring at RT for 2.5 h, further methylmagnesium bromide (1 ml, 3 M in diethyl ether) was added and the mixture was stirred again for 2.5 h. For workup, 1 N hydrochloric acid was added dropwise while cooling with ice, followed by water and ethyl acetate. The organic phase was removed and the water phase was extracted twice more with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered and concentrated. The crude product (1.03 g) was combined with a crude product prepared in the same way (75 mg) and purified using silica gel with dichloromethane-methanol as the eluent. 860 mg of the desired compound were obtained. LC-MS rt: 1.34 min [M+H]+: 304.0 After stirring at RT for 2.5 h the mixture was stirred again for 2.5 h while cooling with ice The organic phase was removed the water phase was extracted twice more with ethyl acetate The combined ethyl acetate phases were dried over sodium sulfate filtered concentrated prepared in the same way (75 mg) purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 3-substituted phthalimidines of formula (I) wherein Z is OH can be prepared by reacting, under nondehydrating conditions, equivalent amounts of a 3-substituted phthalide of the formula ##STR3## wherein R, X, Y, a and b have the same meanings as above, and ammonia, or a primary aliphatic or aromatic amine. The reaction is preferably carried out in the presence of an inert organic solvent for the phthalide such as tetrahydrofuran, diethyl ether, diisopropyl ether, methyl n-butyl ether and the like. The solvent should have a boiling point below about 100° C. to permit ready separation from the reaction product by distillation at moderate temperatures. This serves to minimize dehydration of the 3-hydroxy group on the phthalimidine product. The primary amines employed in the reaction are those of the formula H2N--Q where Q has the same meaning as above. When the reaction is conducted at temperatures above about 100° C., dehydration takes place to produce a 3-substituted phthalimidine of formula (II). can be prepared separation from the reaction product by distillation at moderate temperatures is conducted at temperatures above about 100° C., dehydration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.2 g) was dissolved in absolute THF (30 ml) and stirred at 0° C. with lithium hexamethyldisilazide (721 μl; density: 0.8 g/1; 23% in tent-butyl methyl ether) for 30 min. At 0° C., methylmagnesium bromide (2.87 ml, 3 M in diethyl ether) was then added dropwise while stirring. After stirring at RT for 2.5 h, further methylmagnesium bromide (1 ml, 3 M in diethyl ether) was added and the mixture was stirred again for 2.5 h. For workup, 1 N hydrochloric acid was added dropwise while cooling with ice, followed by water and ethyl acetate. The organic phase was removed and the water phase was extracted twice more with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered and concentrated. The crude product (1.03 g) was combined with a crude product prepared in the same way (75 mg) and purified using silica gel with dichloromethane-methanol as the eluent. 860 mg of the desired compound were obtained. LC-MS rt: 1.34 min [M+H]+: 304.0 After stirring at RT for 2.5 h the mixture was stirred again for 2.5 h while cooling with ice The organic phase was removed the water phase was extracted twice more with ethyl acetate The combined ethyl acetate phases were dried over sodium sulfate filtered concentrated prepared in the same way (75 mg) purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 3-substituted phthalimidines of formula (I) wherein Z is OH can be prepared by reacting, under nondehydrating conditions, equivalent amounts of a 3-substituted phthalide of the formula ##STR3## wherein R, X, Y, a and b have the same meanings as above, and ammonia, or a primary aliphatic or aromatic amine. The reaction is preferably carried out in the presence of an inert organic solvent for the phthalide such as tetrahydrofuran, diethyl ether, diisopropyl ether, methyl n-butyl ether and the like. The solvent should have a boiling point below about 100° C. to permit ready separation from the reaction product by distillation at moderate temperatures. This serves to minimize dehydration of the 3-hydroxy group on the phthalimidine product. The primary amines employed in the reaction are those of the formula H2N--Q where Q has the same meaning as above. When the reaction is conducted at temperatures above about 100° C., dehydration takes place to produce a 3-substituted phthalimidine of formula (II). can be prepared separation from the reaction product by distillation at moderate temperatures is conducted at temperatures above about 100° C., dehydration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure outlined in Example 3, 1-azabicyclo[2.2.2]oct -4-yl(diphenyl)methanol (0.0638 g, 0.217 mmol) and bromomethane (2.0 M in t -Butylmethyl ether, 0.250 mL, 0.500 mmol) in 2 CH3CN/3CHCl3 (4.0 mL) were reacted to give the desired product (0.0739 g, 88.0%). ELMS m/z 308(M+) Rt (1.58 min). were reacted

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.2 g) was dissolved in absolute THF (30 ml) and stirred at 0° C. with lithium hexamethyldisilazide (721 μl; density: 0.8 g/1; 23% in tent-butyl methyl ether) for 30 min. At 0° C., methylmagnesium bromide (2.87 ml, 3 M in diethyl ether) was then added dropwise while stirring. After stirring at RT for 2.5 h, further methylmagnesium bromide (1 ml, 3 M in diethyl ether) was added and the mixture was stirred again for 2.5 h. For workup, 1 N hydrochloric acid was added dropwise while cooling with ice, followed by water and ethyl acetate. The organic phase was removed and the water phase was extracted twice more with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered and concentrated. The crude product (1.03 g) was combined with a crude product prepared in the same way (75 mg) and purified using silica gel with dichloromethane-methanol as the eluent. 860 mg of the desired compound were obtained. LC-MS Rt: 1.34 min [M+H]+:304.0 After stirring at RT for 2.5 h the mixture was stirred again for 2.5 h while cooling with ice The organic phase was removed the water phase was extracted twice more with ethyl acetate The combined ethyl acetate phases were dried over sodium sulfate filtered concentrated prepared in the same way (75 mg) purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: P(OEt)3 was added dropwise to a mixture of tent-butyl methyl ether 55 mL) and potassium tert-butoxide (4.65 g, 41.4 mmol) under a nitrogen atmosphere at 20-30° C. 4-Benzyloxybenzaldehyde (4.61 g, 21.7 mmol) was added in portions to this mixture at 5° C. followed by the addition of tert-butyl alcohol (6.70 g). The reaction mixture was allowed to reach 15° C. and stirred at this temperature for approximately 30 min, after which the reaction was completed (as judged by TLC). Water (30 mL) was added at 5-10° C., and the phases were allowed to separate. The organic phase was concentrated in vacuo, and ethanol (30 mL) was added to the stirred solution. After crystallization had occurred, water (18 mL) was added to the suspension. The light-yellow title compound was filtered off, washed with ethanol/water (1:1 v/v), and dried in vacuo to yield 6.52 g (92% yield). to reach 15° C. to separate The organic phase was concentrated in vacuo, and ethanol (30 mL) was added to the stirred solution After crystallization water (18 mL) was added to the suspension The light-yellow title compound was filtered off washed with ethanol/water (1:1 v/v) dried in vacuo to yield 6.52 g (92% yield)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 24 g of the product of step (ii) 21.5 g bromobutyric acid ethyl ester and 30 ml t.butyl methyl ether are added dropwise over 50 mins. at 5° C. to a pre-prepared suspension of sodium methylate in 25 ml t.butyl methyl ether. The reaction mixture is stirred for 45 mins. at ca. 5° C. and then stirred for 12 hrs. at room temperature. The pH is adjusted to 5 by addition of glacial acetic acid and the obtained suspension diluted with H2O and extracted 3× with t.butyl methyl ether. The organic phase is extracted with NaHCO3 (1×) and brine (1×), and evaporated to ca. 100 ml. 13.5 ml 50% aqueous NaOH are added drop-wise and the whole stirred for 2 hrs. at 40° C., diluted with 50 ml. H2O and stirred for a further 30 mins. at room temperature. The organic phase is separated and the aqueous phase adjusted to pH 1 at max. 40° C. with 15 ml conc. HCl. The reaction mixture is stirred at 40° C. for a further 1.5 hrs., cooled to room temperature and extracted with toluene. The organic phase is washed with NaHCO3 and brine, dried over Na2SO4, filtered and evaporated to yield the title compound as an oil. at ca. 5° C. and then stirred for 12 hrs at room temperature extracted 3× with t The organic phase is extracted with NaHCO3 (1×) and brine (1×) evaporated to ca. 100 ml 13.5 ml 50% aqueous NaOH are added drop-wise the whole stirred for 2 hrs at 40° C., diluted with 50 ml H2O and stirred for a further 30 mins at room temperature The organic phase is separated 40° C. The reaction mixture is stirred at 40° C. for a further 1.5 hrs extracted with toluene The organic phase is washed with NaHCO3 and brine dried over Na2SO4 filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.2 g) was dissolved in absolute THF (30 ml) and stirred at 0° C. with lithium hexamethyldisilazide (721 μl; density: 0.8 g/1; 23% in tent-butyl methyl ether) for 30 min. At 0° C., methylmagnesium bromide (2.87 ml, 3 M in diethyl ether) was then added dropwise while stirring. After stirring at RT for 2.5 h, further methylmagnesium bromide (1 ml, 3 M in diethyl ether) was added and the mixture was stirred again for 2.5 h. For workup, 1 N hydrochloric acid was added dropwise while cooling with ice, followed by water and ethyl acetate. The organic phase was removed and the water phase was extracted twice more with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered and concentrated. The crude product (1.03 g) was combined with a crude product prepared in the same way (75 mg) and purified using silica gel with dichloromethane-methanol as the eluent. 860 mg of the desired compound were obtained. LC-MS rt: 1.34 min [M+H]+: 304.0 After stirring at RT for 2.5 h the mixture was stirred again for 2.5 h while cooling with ice The organic phase was removed the water phase was extracted twice more with ethyl acetate The combined ethyl acetate phases were dried over sodium sulfate filtered concentrated prepared in the same way (75 mg) purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 3-substituted phthalimidines of formula (I) wherein Z is OH can be prepared by reacting, under nondehydrating conditions, equivalent amounts of a 3-substituted phthalide of the formula ##STR3## wherein R, X, Y, a and b have the same meanings as above, and ammonia, or a primary aliphatic or aromatic amine. The reaction is preferably carried out in the presence of an inert organic solvent for the phthalide such as tetrahydrofuran, diethyl ether, diisopropyl ether, methyl n-butyl ether and the like. The solvent should have a boiling point below about 100° C. to permit ready separation from the reaction product by distillation at moderate temperatures. This serves to minimize dehydration of the 3-hydroxy group on the phthalimidine product. The primary amines employed in the reaction are those of the formula H2N--Q where Q has the same meaning as above. When the reaction is conducted at temperatures above about 100° C., dehydration takes place to produce a 3-substituted phthalimidine of formula (II). can be prepared separation from the reaction product by distillation at moderate temperatures is conducted at temperatures above about 100° C., dehydration